3-(4-aminophenyl)-1,2-dihydro-quinoxaline-2-one | 53866-03-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 3-(4-aminophenyl)-1,2-dihydro-quinoxaline-2-one
• 英文别名: 3-p-Anilino-chinoxalon；3-(4-amino-phenyl)-1H-quinoxalin-2-one；3-(4'-Aminophenyl)-2-quinoxalone；3-(4-aminophenyl)-1H-quinoxalin-2-one
• CAS: 53866-03-8
• 化学式: C₁₄H₁₁N₃O
• 分子量: 237.261
• InChiKey: VYQWPGFZVIDNBQ-UHFFFAOYSA-N

物化性质

• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  67.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-aminophenyl)-1,2-dihydro-quinoxaline-2-one 在 盐酸 、 一水合肼 、 sodium nitrite 作用下， 以 甲醇 为溶剂， 反应 4.5h， 生成 3-{4-[(3,5-diamino-pyrazol-4-yl)-azo]-phenyl}-1,2-dihydro-quinoxaline-2-one
  参考文献：
  名称：

  4-Arylazo-3,5-diamino-1H-pyrazole CDK Inhibitors:  SAR Study, Crystal Structure in Complex with CDK2, Selectivity, and Cellular Effects

  摘要：

  In a routine screening of our small-molecule compound collection we recently identified 4-arylazo-3,5-diamino-1H-pyrazoles as a novel group of ATP antagonists with moderate potency against CDK2-cyclin E. A preliminary SAR study based on 35 analogues suggests ways in which the pharmacophore could be further optimized, for example, via substitutions in the 4-aryl ring. Enzyme kinetics studies with the lead compound and X-ray crystallography of an inhibitor-CDK2 complex demonstrated that its mode of inhibition is competitive. Functional kinase assays confirmed the selectivity toward CDKs, with a preference for CDK9cyclin T1. The most potent inhibitor, 4-[(3,5-diamino-1H-pyrazol-4-yl) diazenyl] phenol 31b (CAN508), reduced the frequency of S-phase cells of the cancer cell line HT-29 in antiproliferation assays. Further observed cellular effects included decreased phosphorylation of the retinoblastoma protein and the C-terminal domain of RNA polymerase II, inhibition of mRNA synthesis, and induction of the tumor suppressor protein p53, all of which are consistent with inhibition of CDK9.

  DOI：

  10.1021/jm0605740
• 作为产物：
  描述：

  p-acetylaminophenylglyoxylic acid 在 氢氧化钾 作用下， 以 乙醇 、 水 为溶剂， 反应 4.08h， 生成 3-(4-aminophenyl)-1,2-dihydro-quinoxaline-2-one
  参考文献：
  名称：

  带有6-氮杂嘧啶循环的某些异构喹喔啉衍生物的合成†

  摘要：

  通过将3-（2-氨基苯基）-1,2-二氢喹喔啉1c，3-（4-氨基苯基）-异构体2c，3-（2-氨基苄基）-1，2-二氢喹喔啉-2-one 3c及其重氮化3-（4-氨基苄基）-异构体4c，并通过将形成的重氮盐与氰基乙酰氨基甲酸乙酯偶氮偶合，制备相应的ld-1d。这些化合物的环化提供了在其分子中包含两个带有酸性NH基团的杂环的化合物：3- [2-（5-氰基-6-氮杂嘧啶-1-基）-苯基] -1,2-二氢喹喔啉-2-one 1e，其4-异构体2e，3- [2-（5-氰基-6-氮杂嘧啶-1-基）-苄基] -1,2-二氢喹喔啉-2-one 3e及其4-异构体4e。氨基衍生物图1C是通过反应制得Ñ -acetylisatine与邻苯二胺，并通过制备的水解Ñ -acetylderivative 1A。的氨基衍生物2C是由4- acetylaminophenylglyoxylic酸与邻苯二胺的缩合，并通过制备的水解制备Ñ

  DOI：

  10.1002/jhet.5570380633

文献信息

• 4-Arylazo-3,5-diamino-1<i>H</i>-pyrazole CDK Inhibitors:  SAR Study, Crystal Structure in Complex with CDK2, Selectivity, and Cellular Effects
  作者：Vladimír Kryštof、Petr Cankař、Iveta Fryšová、Jan Slouka、George Kontopidis、Petr Džubák、Marián Hajdúch、Josef Srovnal、Walter F. de Azevedo、Martin Orság、Martina Paprskářová、Jakub Rolčík、Aleš Látr、Peter M. Fischer、Miroslav Strnad

  DOI：10.1021/jm0605740

  日期：2006.11.1

  In a routine screening of our small-molecule compound collection we recently identified 4-arylazo-3,5-diamino-1H-pyrazoles as a novel group of ATP antagonists with moderate potency against CDK2-cyclin E. A preliminary SAR study based on 35 analogues suggests ways in which the pharmacophore could be further optimized, for example, via substitutions in the 4-aryl ring. Enzyme kinetics studies with the lead compound and X-ray crystallography of an inhibitor-CDK2 complex demonstrated that its mode of inhibition is competitive. Functional kinase assays confirmed the selectivity toward CDKs, with a preference for CDK9cyclin T1. The most potent inhibitor, 4-[(3,5-diamino-1H-pyrazol-4-yl) diazenyl] phenol 31b (CAN508), reduced the frequency of S-phase cells of the cancer cell line HT-29 in antiproliferation assays. Further observed cellular effects included decreased phosphorylation of the retinoblastoma protein and the C-terminal domain of RNA polymerase II, inhibition of mRNA synthesis, and induction of the tumor suppressor protein p53, all of which are consistent with inhibition of CDK9.
• Synthesis of some isomeric quinoxaline derivatives with 6-azauracil cycle
  作者：Iveta Wiedermannová、Jan Slouka

  DOI：10.1002/jhet.5570380633

  日期：2001.11

  By diazotization of 3-(2-aminophenyl)-1,2-dihydroquinoxaline 1c, its 3-(4-aminophenyl)-isomer2c, 3-(2-aminobenzyl)-1,2-dihydroquinoxaline-2-one 3c and its 3-(4-aminobenzyl)-isomer 4c and by azo coupling of formed diazonium salts with ethyl cyanoacetylcarbamate, corresponding hydrazones ld-4d were prepared. Cyclization of these compounds afforded compounds containing two heterocyclic rings with acidic

  通过将3-（2-氨基苯基）-1,2-二氢喹喔啉1c，3-（4-氨基苯基）-异构体2c，3-（2-氨基苄基）-1，2-二氢喹喔啉-2-one 3c及其重氮化3-（4-氨基苄基）-异构体4c，并通过将形成的重氮盐与氰基乙酰氨基甲酸乙酯偶氮偶合，制备相应的ld-1d。这些化合物的环化提供了在其分子中包含两个带有酸性NH基团的杂环的化合物：3- [2-（5-氰基-6-氮杂嘧啶-1-基）-苯基] -1,2-二氢喹喔啉-2-one 1e，其4-异构体2e，3- [2-（5-氰基-6-氮杂嘧啶-1-基）-苄基] -1,2-二氢喹喔啉-2-one 3e及其4-异构体4e。氨基衍生物图1C是通过反应制得Ñ -acetylisatine与邻苯二胺，并通过制备的水解Ñ -acetylderivative 1A。的氨基衍生物2C是由4- acetylaminophenylglyoxylic酸与邻苯二胺的缩合，并通过制备的水解制备Ñ